| First Author | Koeberle A | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 7 | Pages | 2546-51 |
| PubMed ID | 23359699 | Mgi Jnum | J:194324 |
| Mgi Id | MGI:5473440 | Doi | 10.1073/pnas.1216182110 |
| Citation | Koeberle A, et al. (2013) Arachidonoyl-phosphatidylcholine oscillates during the cell cycle and counteracts proliferation by suppressing Akt membrane binding. Proc Natl Acad Sci U S A 110(7):2546-51 |
| abstractText | The activity of protein kinase B (Akt)--a major kinase promoting cell proliferation and survival--oscillates during the cell cycle. To investigate whether membrane phospholipids may regulate Akt phosphorylation and thus activity, we monitored the lipid profile of nocodazole-synchronized mouse NIH 3T3 fibroblasts during the cell cycle by liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). The proportion of sn-2-arachidonoyl-phosphatidylcholine (20:4-PC) inversely correlated with Akt activity. Increasing the cellular ratio of 20:4-PC by supplementation of 20:4-PC to the cell culture medium diminished Akt [serine (Ser)473] phosphorylation. Saturated and monounsaturated phosphatidylcholines, used as control had no effect; 20:4-PC reduced cell proliferation relative to controls, interfered with S-phase transition, and suppressed Akt downstream signaling and cyclin expression like LY294002, which is a specific inhibitor of the phosphatidylinositol-3-kinase/Akt pathway. Additive effects of 20:4-PC and LY294002 were not observed, underlining the critical role of Akt for 20:4-PC signaling; 20:4-PC suppressed Akt membrane translocation as shown by immunofluorescence microscopy but left the concentration of the anchor lipid phosphatidylinositol-3,4,5-trisphosphate unchanged. An in vitro binding assay suggests that 20:4-PC attenuates the interaction of Akt with its membrane binding site. We conclude that 20:4-PC oscillates during the cell cycle and delays cell cycle progression by inhibiting Akt membrane binding. |
